Alzheimer's Disease (AD) and Senile Dementia of the Alzheimers Type (SDAT), with over one million individuals affected in the United States alone, are the most common causes of dementia in middle and late life, respectively. One of the more striking changes in the brains of patients with AD/SDAT is a profound reduction in the activity of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) in the cerebral cortex and hippocampus. While the basis for this reduction in cholinergic activity had been unclear, recent evidence has been obtained to suggest that the deficiency may be due to the selective loss of cholinergic positive neurons in the nucleus basalis of Meynert (nbM). The nbM, which constitutes part of the substantia innominata (SI) consists of large cholinergic positive neurons which have direct projections to the cerebral cortex. It has now been documented that the majority of these neurons undergo severe degeneration in patients with AD or SDAT, thus providing a pathological basis for the depletion of cortical cholinergic activity. However, the cognitive impairments associated with AD/SDAT, the most striking of which is a severe memory loss, have yet to be attributed directly to any specific neuropathology. Indeed, virtually nothing is known about the behavioral consequences of selective damage to the nbM or substantia innominata. It is the intent of this proposal to study directly the effects of lesions of the nbM and substantia innominata in the rhesus monkey, by assessing, in the same animals, both the extent of memory impairment and depletion of cortical cholinergic activity. The specific aims of this proposal will be: 1) to assess the effects of bilateral SI lesions on the post-operative retention of a preoperatively acquired recognition task; 2) to assess the consequences of this lesion on postoperative performance of recognition memory as a function of delays and interference, to which patients with AD/SDAT are particularly sensitive; 3) to determine the level of reduction in cholinergic activity in the projection targets of the SI using scanning and integrating microdensitometry; 4) to assess any possible relationship between the extent of behavioral deficit with changes in cortical cholinergic activity in the brain; 5) to compare behavioral data obtained from this study with that obtained from studies in monkeys with selective hippocampal damage, another major structure which undergoes extensive pathological changes in AD/SDAT.